We have previously reported that p53 is highly upregulated by mutant Huntingtin (Htt) containing expanded polyglutamine repeats both in a HD cell model (PC12 cells with Htt) and Htt transgenic animals, which conferrs increased p53-mediated gene expression. We also reported that deletion of p53 increases cellular viability in HD cell model as well as normalized impaired behavior during rotarod tasks and reduced hyperactivity in rotational movements which are found in HD animal models (Bae et al, 2001, SFN Abstract). Here we present additional data to support roles of p53 in HD animal models: a reduced mortality and restoration of impaired pre-pulse inhibition in mutant Htt transgenic mice upon partial deletion of p53. Based on our previous finding that HD patient lymphoblasts display vulnerability in mitochondrial depolarization (Sawa et al,1999, Nat. Med.), we have analyzed mitochondrial membrane potential as an underling mechanism. We observed mitochondrial depolarization in PC12 cells expressing mutant H...